Although much is known about the regulation of cardiac function by the extrinsic cardiac nerves, very little is presently known about the intrinsic cardiac innervation; i.e., postganglionic parasympathetic neurons and adrenergic chromaffin cells. Recently, we have been able to specifically activate the former and assess their negative effects on cardiac contractility. We have not yet been able to show that chromaffin cell elements, however, have any effect on contractility. The extent to which either of these neural elements can modify cardiac electrical activity is not known. The objective of the proposed research is to determine the capacity of this intrinsic system to modify cardiac impulse generation and/or conduction. The methods involve direct surface recording from all major areas of the cardiac conduction system in normal and cardiac-denervated dogs. The electrical activity of the atrium, His bundle and basal ventricular septum will be recorded using an intra-arterial catheter electrode. Recordings from ventricular Purkinje fibers and adjacent ventricular muscle will be done with a plunge-wire technique. Recordings will be made from the major bundle branches and other septal conduction elements under open-heart conditions using total cardiopulmonary bypass. The intrinsic cardiac innervation will be specifically activatd by intracoronary injection of nicotine and verified by subsequent blockade with d-tubocurare or tetrodotoxin. Chromaffin cells will be activated by intracoronary nicotine, but after blockade of muscarinic effects with atropine. The experiments will provide: 1) An insight into a previously uninvestigated area of cardiac neural control; 2) Valuable information regarding the potential effects of pharmacologic agents on the heart (e.g., nicotine); 3) The ability to predict the responses of transplanted (i.e., denervated) hearts to drugs which potentially interact with the intrinsic cardiac innervation. BIBLIOGRAPHIC REFERENCES: Priola, D.V. and Cote, I. Differential sensitivity of the canine heart to acetylcholine and vagal stimulation. Amer. J. Physiol., 1977 (in press). Priola, D.V. and Spurgeon, H.A. Cholinergic sensitivity of the denervated heart. Circ. Res., 1977 (in press).